FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms

FLT3 mutations are one of the most common genetic aberrations found in nearly 30% of acute myeloid leukemias (AML). The mutations are associated with poor prognosis despite advances in the understanding of the biological mechanisms of AML. Numerous small molecule FLT3 inhibitors have been developed in an effort to combat AML. Even with the development of these inhibitors, the five-year overall survival for newly diagnosed AML is less than 30%. In 2017, midostaurin received FDA approval to treat AML, which was the first approved FLT3 inhibitor in the U.S. and Europe. Following, gilteritinib received FDA approval in 2018 and in 2019 quizartinib received approval in Japan. This review parallels these clinical success stories along with other pre-clinical and clinical investigations of FLT3 inhibitors.

Automated summary

FLT3 mutations are commonly found in AML and are associated with poor prognosis. Despite the development of FLT3 inhibitors, the five-year overall survival rate for newly diagnosed AML remains low. Midostaurin was the first FDA-approved FLT3 inhibitor in the US and Europe. This review summarizes the clinical success stories and other pre-clinical and clinical investigations of FLT3 inhibitors.